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Where We Go from Here in the Management of Multiple Sclerosis

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Where We Go from Here in the Management of Multiple Sclerosis PERSPECTIVES IN MS Beyond Efficacy and Safety: Where We Go From Here in the Management of Multiple Sclerosis Introduction radiologically isolated syndrome (RIS) who are at high When selecting a disease-modifying therapy (DMT) for risk for the development of clinically definite MS (CDMS) patients with multiple sclerosis (MS), clinicians must first should also be treated with DMTs as soon as possible. consider the efficacy and safety of the agent.1 Other consid- Several clinical trials have provided proof of concept for erations include initiating treatment as early as possible, an early window of initial treatment intervention in patients adherence to current and subsequent DMTs, under- with CIS.9 Significant reductions in the risk for developing standing when to switch patients from their current DMTs CDMS were observed with the use of interferon beta agents to other medications (and knowing when not to switch), and glatiramer acetate when treatment was initiated early and cost factors.2-5 on. Physical disability and number and/or volume of brain Although the currently approved DMTs are reliable, lesions were also improved with early treatment. Similar constantly being improved, effective in treating relapses, results have been reported with some of the newer DMTs, and able to reduce long-term disability, they have only such as teriflunomide, alemtuzumab, and fingolimod. limited efficacy in treating progressive disease that is not associated with inflammatory relapses.6 More effective Adherence to Disease-Modifying Therapies DMTs are needed specifically for patients with primary According to the World Health Organization (WHO), progressive MS. Likewise, agents that repair or regenerate adherence is defined as “the extent to which a person’s neurons, oligodendrocytes, and supporting glia are essen- behavior—taking medication, following a diet, and/or tial for effective treatment.7 executing lifestyle changes— corresponds with agreed Several new medications have entered the market in recommendations from a health care provider.”10,11 There recent years and others are in late-phase clinical studies are 3 distinct components of adherence: (1) acceptance, (2) for the treatment of patients with relapsing or progressive persistence, and (3) compliance.10,12 Patients must accept forms of MS.8 These agents represent a variety of mecha- that they need treatment, they must persist in taking the nisms of action, providing not only lower relapse rates but treatment over time, and they must comply with their also improvement in disabilities. prescribed treatment (that is, take the right dose at the right time and with the correct frequency). Importance of Early Diagnosis and Early Treatment Medication adherence is a major concern in the MS MS is characterized by both inflammation and progres- population, particularly with DMTs.10,12,13 The WHO sive neuroaxonal damage.9 Although this damage often estimates an average adherence rate of only 50% among occurs in the early stages of disease, it may be masked by compensatory Brain Atrophy Occurs Early in the Disease Process mechanisms. Thus, progressive damage Figure 1. may go unrecognized until it is too late for intervention to be beneficial. As MS progresses, the balance between the degenerative and the reparative processes shifts, resulting in progres- sive neuroaxonal degeneration and increasing disability (see Figure 1).9 Because brain atrophy creates permanent damage, and correlates with physical and cognitive disability, it is important for patients with MS to be treated with DMTs as early in the disease course as possible, in order to decrease the loss of brain volume and its effects.2 Additionally, patients with Figure reprinted with permission from the Multiple Sclerosis Foundation and EW Associates, LLC. clinically isolated syndrome (CIS) and 20 MARCH 2018 AJMC® Perspectives PERSPECTIVES IN MS chronically ill patients in the developed Figure 2. The Benefits of Adherence10 world.10,13 Although overall rates of adher- Clinician Benefits ence to DMTs in patients with MS is Lower risk for relapse estimated to be higher than 50%,10,12 varia- Improved QoL tions among studies and medications do Patient Benefits exist. Suboptimal adherence to DMTs has a Lower risk for relapse Better QoL Payer Benefits negative impact on patient morbidity and Higher treatment satisfaction Lower medical costs Fewer hospitalizations Fewer hospitalization mortality outcomes, as well as on overall Fewer ED visits Fewer ED visits costs of patient care.1,10 Some of the major Less work loss benefits associated with patient adherence Societal Benefits to therapy are displayed in Figure 2. Improvements in productivity Four recent studies have evaluated Less work loss due to sick days and disability adherence rates with the first-generation, ED indicates emergency department; QoL, quality of life. injectable DMTs (including interferon beta-1b, intramuscular interferon beta-1a, subcutaneous interferon beta-1a, and glatiramer acetate) (AEs) associated with the agent, and fear/anxiety over using used in the treatment of MS.13-16 injections.10,11 A number of different approaches might help to improve adherence among patients with MS. • In a population-based cohort study of 4830 patients, optimal adherence was observed in 76% of patients • Enlist support from family members and/ after 1 year of therapy.13 Patients who initiated or caregivers.10 therapy in recent years were more likely to have • For patients who experience cognitive impairment suboptimal adherence and to discontinue their DMT and those who frequently forget to take their medi- within the first 12 months versus those who began cation, efforts should be made to simplify treatment treatment in earlier years. regimens.10 Medications that can be adminis- • In a systematic review of medication adherence tered fewer versus more times per day should be from 24 studies with a combined population of suggested, and monotherapy options rather than >2400 patients, 59.6% of patients were adherent to combination therapies should be recommended. therapy.14 Common barriers to adherence included • Establish realistic expectations about the potential patients forgetting to their take medication, benefits of treatment.1,12 Patients should under- perceived lack of efficacy, anxiety about injections, stand that DMTs do not “cure” MS, that they may and adverse reactions. not eliminate MS symptoms, and that they may not • In a multicenter, observational study of 798 completely eradicate future disease activity. patients, nonadherence was reported by 36% to • Evaluate the economic burden on patients associ- 39% of patients surveyed.15 Forgetting to admin- ated with the use of MS medications.10,11 Providers ister their injections, which was the most common should have an improved understanding of formu- reason cited by participants for nonadherence, lary issues, such as the selection of agents that are was reported by 58% of those with adherence available on the formulary, the formulary override issues. Other reasons for nonadherence included process, prior authorization, initiation and ongoing injection-site reactions, effects on quality of life, and approval, and adherence to Risk Evaluation and symptoms of depression. Mitigation Strategies (REMS), where needed.5 • Of the 2648 patients evaluated in the Global Additionally, support from a social worker can be Adherence Project, 75% were adherent to therapy.16 helpful, along with enlisting aid from the manufac- The most common reported reasons for nonadher- turer. Medication assistance programs exist for all of ence included forgetting to administer the injection the FDA-approved DMTs. and other injection-related reasons. Provide injection training for injectable DMTs.10-12 For Adherence is difficult to quantify.10 In many cases, there example, patients should be trained to rotate injection can be multiple contributing factors to poor adherence sites, to use an autoinjector (which is available free of versus only one factor. Clinical trial data have identified a charge from manufacturers), to inject medications at room myriad of contributing factors that lead to poor adherence, temperature, to ice the area before and after injecting including cognitive impairment, perceived lack of efficacy medication, and to massage the area following injection from DMTs, economic/financial challenges, adverse events (for interferon beta products only). AJMC® Perspectives MARCH 2018 21 PERSPECTIVES IN MS Manage AEs accordingly.10-12 Remind patients using switching should be considered earlier than later, because interferon beta agents that flulike symptoms often improve residual impairment may worsen with each new relapse. with time, and can be relieved by premedication with It is also important to recognize that switching DMTs may nonsteroidal anti-inflammatory drugs or acetaminophen. lead to breakthrough disease, particularly with longer- The impact of flulike symptoms may also be reduced by acting products. administering the agent in the evening, before bed, on the Other considerations (besides risks/benefits, which weekend, or before another convenient period of time. have been discussed previously) when switching thera- For patients who experience poor treatment adherence pies include the following: immunogenicity; mechanism because of anxiety or fear over administering injections, of action of prior DMTs, which can affect the efficacy and consider switching to an oral therapy.11 safety of subsequent therapies; risk for progressive multi-
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